Genetic Variant CSN1S1:c.106-4G>T (chr4-69935922-G-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001890.2(CSN1S1):c.106-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CSN1S1
NM_001890.2 splice_region, intron

Scores

Splicing: ADA: 0.00001582

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.96

Variant links:

Genes affected

CSN1S1 (HGNC:2445): (casein alpha s1) Predicted to be involved in response to dehydroepiandrosterone; response to estradiol; and response to steroid hormone. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

CSN1S1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 4-69935922-G-T is Benign according to our data. Variant chr4-69935922-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 773695.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSN1S1	NM_001890.2 link	c.106-4G>T		splice_region_variant, intron_variant	Intron 4 of 15	ENST00000246891.9	NP_001881.1	P47710-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CSN1S1	ENST00000246891.9 link	c.106-4G>T	splice_region_variant, intron_variant	Intron 4 of 15	1	NM_001890.2	ENSP00000246891.4	P47710-1
CSN1S1	ENST00000507772.5 link	c.106-4G>T	splice_region_variant, intron_variant	Intron 3 of 13	5		ENSP00000427490.1	E9PDQ1
CSN1S1	ENST00000507763.5 link	c.106-4G>T	splice_region_variant, intron_variant	Intron 3 of 13	5		ENSP00000422611.1	P47710-4
CSN1S1	ENST00000505782.5 link	c.106-4G>T	splice_region_variant, intron_variant	Intron 3 of 12	5		ENSP00000426684.1	D6RF34

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149120

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000246

AC:

AN:

1340142

Hom.:

Cov.:

AF XY:

0.0000241

AC XY:

AN XY:

662706

show subpopulations

Gnomad4 AFR exome

AF:

0.0000689

Gnomad4 AMR exome

AF:

0.000331

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000578

Gnomad4 SAS exome

AF:

0.0000541

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000125

Gnomad4 OTH exome

AF:

0.0000180

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

149120

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72564

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000429

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.038

DANN

Benign

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over